Epigenetic clock and methylation studies in vervet monkeys

Abstract

DNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, we developed two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes that gain methylation with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED and genes possessing the trimethylated H3K27 mark in their promoters. The epigenetic clocks are expected to be useful for anti-aging studies in vervets.

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“…This would introduce a bias that would have affected the results. As such, we used liver data from another primate: the vervet monkey, whose liver samples were profiled uniformly across the entire lifespan 24 . The vervet monkey exhibits a substantially longer maximum lifespan than the house mouse (30.8 yr versus 4 yr according to the 'anAge' database 25 ).…”

“…The data from other species are presented in other publications 42 (vervet monkey, ref. 24 ; mice, ref. 43 ).…”

“…Details on the n = 1,211 human tissue samples (adipose, blood, bone marrow, dermis, epidermis, heart, keratinocytes, fibroblasts, kidney, liver, lung, lymph node, muscle, pituitary, skin, spleen) can be found in refs. 24,44 . Human postmortem tissue and organ samples were obtained from the National NeuroAIDS Tissue Consortium 45 .…”

“…Details on the n = 48 liver samples from vervet monkey data (whose ages ranged between zero and 21.8 yr) can be found in ref. 24 .…”

“…The human methylation data, vervet monkey data and mouse data were not generated for this study. These data will be presented in other publications (humans and primates 42 , vervet monkey 24 , mice 43 ) and can be requested from S.H. All data from the Mammalian Methylation Consortium will be made publicly available.…”